Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase
Huang, J; Welch, J; Ricote, M; Binder, C; Willson, T; Kelly, C; Witztum, J; Funk, C; Conrad, D; Glass, C
HERO ID
704426
Reference Type
Journal Article
Year
1999
Language
English
PMID
| HERO ID | 704426 |
|---|---|
| In Press | No |
| Year | 1999 |
| Title | Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase |
| Authors | Huang, J; Welch, J; Ricote, M; Binder, C; Willson, T; Kelly, C; Witztum, J; Funk, C; Conrad, D; Glass, C |
| Journal | Nature |
| Volume | 400 |
| Issue | 6742 |
| Page Numbers | 378-382 |
| Abstract | The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of critical aspects of development and homeostasis, including adipocyte differentiation, glucose metabolism and macrophage development and function. PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated fatty acids, 15-deoxy-delta prostaglandin J2 and components of oxidized low-density lipoprotein, such as 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE). However, the identities of endogenous ligands for PPAR-gamma and their means of production in vivo have not been established. In monocytes and macrophages, 13-HODE and 15-HETE can be generated from linoleic and arachidonic acids, respectively, by a 12/15-lipoxygenase that is upregulated by the TH2-derived cytokine interleukin-4. Here we show that interleukin-4 also induces the expression of PPAR-gamma and provide evidence that the coordinate induction of PPAR-gamma and 12/15-lipoxygenase mediates interleukin-4-dependent transcription of the CD36 gene in macrophages. These findings reveal a physiological role of 12/15-lipoxygenase in the generation of endogenous ligands for PPAR-gamma, and suggest a paradigm for the regulation of nuclear receptor function by cytokines. |
| Doi | 10.1038/22572 |
| Pmid | 10432118 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |